Peripheral peroxisomal ß-oxidation engages neuronal serotonin signaling to drive stress-induced aversive memory in C. elegans.
Cell Rep
; 43(4): 113996, 2024 Apr 23.
Article
in En
| MEDLINE
| ID: mdl-38520690
ABSTRACT
Physiological dysfunction confers negative valence to coincidental sensory cues to induce the formation of aversive associative memory. How peripheral tissue stress engages neuromodulatory mechanisms to form aversive memory is poorly understood. Here, we show that in the nematode C. elegans, mitochondrial disruption induces aversive memory through peroxisomal ß-oxidation genes in non-neural tissues, including pmp-4/very-long-chain fatty acid transporter, dhs-28/3-hydroxylacyl-CoA dehydrogenase, and daf-22/3-ketoacyl-CoA thiolase. Upregulation of peroxisomal ß-oxidation genes under mitochondrial stress requires the nuclear hormone receptor NHR-49. Importantly, the memory-promoting function of peroxisomal ß-oxidation is independent of its canonical role in pheromone production. Peripheral signals derived from the peroxisomes target NSM, a critical neuron for memory formation under stress, to upregulate serotonin synthesis and remodel evoked responses to sensory cues. Our genetic, transcriptomic, and metabolomic approaches establish peroxisomal lipid signaling as a crucial mechanism that connects peripheral mitochondrial stress to central serotonin neuromodulation in aversive memory formation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidation-Reduction
/
Signal Transduction
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Serotonin
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Caenorhabditis elegans
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Peroxisomes
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Caenorhabditis elegans Proteins
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Memory
Limits:
Animals
Language:
En
Journal:
Cell Rep
/
Cell reports
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: